PXD018972

PXD018972 is an original dataset announced via ProteomeXchange.

Title	Caspr2 interacts with type 1 inositol 1,4,5-trisphosphate receptor in the developing cerebellum and regulates Purkinje cell morphology
Description	Contactin-associated protein-like 2 (Caspr2) is a neurexin-like protein that has been associated with numerous neurological conditions. However, the mechanisms underlying Caspr2 function in the central nervous system remain incompletely understood. Here, we report on a functional role for Caspr2 in the developing cerebellum. Loss of Caspr2 impairs Purkinje cell dendritic development, alters cell signaling and results in motor coordination deficits. Caspr2 is highly enriched at synaptic specializations in the cerebellum. Using a proteomic approach, we identify type 1 inositol 1,4,5-trisphosphate receptor (IP3R1) as a specific synaptic interaction partner of the Caspr2 extracellular domain (ECD) in the molecular layer (ML) of the developing cerebellum. The interaction of Caspr2 ECD with IP3R1 inhibits IP3R1-mediated changes in cellular morphology. Together, our work defines a mechanism by which Caspr2 controls the development and function of the cerebellum, and advances our understanding of how Caspr2 dysfunction might lead to specific brain disorders.
HostingRepository	PRIDE
AnnounceDate	2020-07-13
AnnouncementXML	Submission_2020-07-20_02:45:14.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Holger Kramer
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	monohydroxylated residue
Instrument	amaZon ETD

Revision	Datetime	Status	ChangeLog Entry
0	2020-05-04 06:18:12	ID requested
1	2020-07-12 23:59:49	announced
⏵ 2	2020-07-20 02:45:15	announced	2020-07-20: Updated publication reference for PubMed record(s): 32675284.

Argent L, Winter F, Prickett I, Carrasquero-Ordaz M, Olsen AL, Kramer H, Lancaster E, Becker EBE, Caspr2 interacts with type 1 inositol 1,4,5-trisphosphate receptor in the developing cerebellum and regulates Purkinje cell morphology. J Biol Chem, 295(36):12716-12726(2020) [pubmed]

submitter keyword: Caspr2

Itpr

inositol 1,4,5-trisphosphate receptor type 1

cerebellum

Purkinje cell

Esther B. E. Becker
contact affiliation	Department of Physiology, Anatomy and Genetics; University of Oxford; Sherrington Road; Oxford, OX1 3PT; United Kingdom
contact email	esther.becker@dpag.ox.ac.uk
lab head
Holger Kramer
contact affiliation	MRC London Institute of Medical Sciences
contact email	h.kramer@lms.mrc.ac.uk
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD018972
     1. Label: PRIDE project
     2. Name: Caspr2 interacts with type 1 inositol 1,4,5-trisphosphate receptor in the developing cerebellum and regulates Purkinje cell morphology